This project assesses the safety and efficacy of pharmacological treatments of cocaine and opioid abuse in clinical trials. Findings of a clinical trial recently completed in our section do not support the utility of carbamazepine in the treatment of cocaine dependence. A double-blind, placebo-controlled clinical trial was completed testing carbamazepine in cocaine dependent subjects. Outcome measures were persent cocaine-negative urine samples, self-reported drug use, and self- reported craving for cocaine. There were no significant differences between subjects randomly assigned to the placebo or carbamazepine treatment groups on any of the primary outcome measures. The administration of carbamazepine to cocaine dependent individuals was safe at the dose tested. Evidence from preclinical studies suggests that the reinforcing effects of cocaine are related to its inhibition of dopamine reuptake. Much of the work to develop pharmacological treatments of cocaine dependence has thus far focused on dopaminergic agents, though no dopaminergic agents have yet been shown to be effective in reducing cocaine use. An open trial testing the safety and efficacy of combination treatment with buproprion and bromocriptine, agents with dopaminergic activity, is underway and has so far shown a low incidence of side effects among treated subjects. This study is the first to apply the strategy of combining pharmacologic agents to increase the efficacy of individual agents in the treatment of cocaine dependence. The partial opiate agonist buprenorphine is a safe and effective treatment for opiate dependence. Some preclinical studies and uncontrolled clinical case series have suggested that buprenorphine might also be effective in reducing cocaine use by opiate addicts. A double- blind, controlled clinical trial is underway that directly evaluates the efficacy of buprenorphine in reducing both opiate and cocaine use in dually opiate- and cocaine-dependent patients. Medically supervised withdrawal from opioids is a commonly used treatment but is usually not effective in establishing long-term abstinence because patients frequently relapse soon after completion of the withdrawal. A procedure for initiating naltrexone maintenance during withdrawal treatment is being developed to provide a more effective post-withdrawal treatment. The efficacy of buprenorphine/naltrexone combinations are being tested in a clinical trial.